Veterinary Research Forum

Abstract Doxorubicin (DOX), as a potent anti-cancer agent, exerts side effects in vital organs. Various chemical compounds with tissue protective properties are used to prevent the side effects of DOX. This study was planned to investigate the effects of histidine (HIS) and N-acetylcysteine (NAC) ​​on DOX-induced acute kidney injury. The possible mechanisms were followed by determining the histopathological changes of the kidney along with the biochemical alterations of the blood and kidney tissue. Forty-eight rats were divided into eight groups of six animals each to receive normal saline and DOX after alone and combined treatments with HIS and NAC. The DOX at a single dose of 15.00 mg kg^-1 was intraperitoneally injected on day one. The separate and combined intraperitoneally injections of HIS and NAC at a similar dose of 100 mg kg^-1 were began 30 min after DOX administration and continued for seven consecutive days. The DOX increased kidney weight and caused congestion, hemorrhages and degeneration in kidney tissue. It also increased serum urea and creatinine concentrations and kidney tissue levels of malondialdehyde, tumor necrosis factor-alpha and caspase-3, and decreased superoxide dismutase activity in this tissue. Separate and combined treatments with HIS and NAC improved all the above-mentioned effects of DOX. The restoring effects of the combined treatment were more prominent than the effect of amino acids alone. It was concluded that anti-oxidative, anti-inflammatory and anti-apoptotic mechanisms might be related to the tissue protective effects of HIS and NAC against DOX-induced acute renal injury.

Abstract Studies conducted on animal models have shown that the administration of glycerol can lead to kidney tissue damage and impaired renal function. This is believed to be caused by oxidative stress and inflammation, which in turn can result in elevated levels of blood urea nitrogen (BUN) and creatinine. These metabolites are commonly used as indicators of renal function. The aim of the current experimental research was to investigate the protective efficacy of ellagic acid in a rat model of rhabdomyolysis induced by glycerol. Sixty healthy adult male Wistar rats weighing between 250 - 300 g were divided into five equal groups including control, rhabdomyolysis (administered 8.00 mL kg^-1 of glycerol), and three rhabdomyolysis plus various doses of ellagic acid (25.00, 50.00 and 100 mg kg^-1 per day; 72 hr after receiving glycerol for 14 days successively) groups. Serum levels of BUN, creatinine, lactate dehydrogenase, alkaline phosphatase, electrolytes and inflammatory cytokines were evaluated in all rats. Histopathological studies were also performed on kidney tissues from all groups. The administration of ellagic acid resulted in a significant increase in renal function biomarkers compared to the rats with acute kidney injury. This increase was consistent with notable reductions in tumor necrosis factor-α levels and increases in interleukin-10 levels observed in blood samples. Furthermore, the improvement in histopathological indices observed in rats received ellagic acid confirmed its nephroprotective role. The results of the current experimental study suggest that ellagic acid can improve kidney damage following glycerol injection, potentially by modulating the inflammatory process.